Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness

Peter W. Y. Chan, Nilmadhab Chakrabarti, Chris Ing, Ondrej Halgas, Terence K. W. To, Marielle Wälti, Alain-Pierre Petit, Christopher Tran, Alexei Savchenko, Alexander F. Yakunin, Elizabeth A. Edwards, Régis Pomès, Emil F. Pai (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

l-2-Haloacid dehalogenases, industrially and environmentally important enzymes that catalyse cleavage of the carbon-halogen bond in S-2-halocarboxylic acids, were known to hydrolyse chlorinated, brominated and iodinated substrates but no activity towards fluorinated compounds had been reported. A screen for novel dehalogenase activities revealed four l-2-haloacid dehalogenases capable of defluorination. We now report crystal structures for two of these enzymes, Bpro0530 and Rha0230, as well as for the related proteins PA0810 and RSc1362, which hydrolyse chloroacetate but not fluoroacetate, all at ∼2.2 Å resolution. Overall structure and active sites of these enzymes are highly similar. In molecular dynamics (MD) calculations, only the defluorinating enzymes sample more compact conformations, which in turn allow more effective interactions with the small fluorine atom. Structural constraints, based on X-ray structures and MD calculations, correctly predict the defluorination activity of the homologous enzyme ST2570.

Original languageEnglish
Article numbere202100414
Number of pages14
JournalChemBioChem
Volume23
Issue number1
Early online date22 Oct 2021
DOIs
Publication statusPublished - 5 Jan 2022

Keywords

  • enzyme catalysis
  • enzymic defluorination
  • L-2-haloacid dehalogenases
  • molecular dynamics
  • protein structures

Fingerprint

Dive into the research topics of 'Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness'. Together they form a unique fingerprint.

Cite this